Significant PK variability of plasma-derived FIX concentrates in chinese children with Haemophilia B: A fixed single-dose study of factor IX-CTBB

Abstract

Background The pharmacokinetics (PK) characters of plasma-derived Factor IX (pdFIX) concentrate in Chinese children with Haemophilia B(HB) have not yet been reported.

Aim To assess the PK parameters of pdFIX in children with severe HB and identify factors that influence FIX PK.

Methods This non-randomized, open-label PK study enrolled children with severe HB (FIX≤2 %). Patients received 50 IU± 5 IU/kg pdFIX (Human coagulation Factor IX-CTBB) after at least 96 h wash-out period. Blood samples for PK assessments were collected before infusion (pre-dose) and at 15 min, 30 min, 1 h, 3 h, 6 h, 9 h, 24 h, 48 h, 72 h and 96 h post-infusion. FIX activity was measured by a one-stage assay.

Results Twenty patients were enrolled with a median age of 8.3 (range 1.8-15.4) years. The peak plasma levels of FIX: C in all patients were observed within 15 min. Their median terminal half-life (t_1/2) was 32.6 (range 23.3-52.0) hours. The median values of in vivo recovery (IVR) at 15 min, clearance (CL), volume of distribution at state (Vss) and area under the curve (AUC) were 1.0 (0.9, 1.2) IU/dL per IU/kg, 5.2 (IQR 4.8, 6.4) mL/h/kg, 207.9 (IQR 183.5, 301.4) mL/kg, 9.77 (IQR 7.76, 11.23) U*h/mL respectively. The t_1/2, Vss and mean residence time after intravenous injection (MRT) decreased with increasing age and body weight. Changes in CL with body weight were similar to t_1/2, but no significant correlation exists with age.

Conclusions There is a significant inter-individual variability in PK profiles among Chinese children with severe HB, which is related to age and body weight changes, indicating the necessity of individualized prophylaxis driven by PK.

Keywords

Haemophilia B / Pharmacokinetics / Children / Plasma-derived FIX

Author contributions

Zhenping Chen and Runhui Wu proposed this study, reviewed the manuscript and approved the submission. Guoqing Liu and Di Ai conducted the PK tests, collected the data, analyzed the data, and wrote the manuscript. Yingzi Zhen and Xinyi Wu helped with blood sampling. Gang Li devoted to laboratory tests. Wanru Yao and Yunyun Wei did some analysis. Zekun Li and Yaohan Zhou collected some data. Guoqing Liu and Di Ai share the co-first authorship of this work. The manuscript has been read and approved for submission by all authors.

Declaration of Competing Interest

The authors confirmed that there are no interests.

Acknowledgment

We thank the patients and their parents. This work was supported by the Beijing Municipal Administration of Hospitals Incubating Program (PX2024043).

Data Availability

The data could be available upon reasonable request to corresponding author.

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